Clonality and life cycles of intestinal crypts explained by a state dependent stochastic model of epithelial stem cell organization
Clonality and life cycles of intestinal crypts explained by a state dependent stochastic model of epithelial stem cell organization
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DOI：
10.1006/jtbi.1996.0340
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发表时间：
1997-05-07
影响因子：
2
通讯作者：
Potten, CS
中科院分区：
文献类型：
--
作者：
Loeffler, M;Bratke, T;Potten, CS
干细胞的组织和控制是上皮细胞生物学的关键问题。小肠鼠隐窝是研究此类问题的有用组织，因为已知干细胞位于隐窝底部的特定位置，在那里它们可以自我维持。最近的数据表明，（1）隐窝中活性干细胞的数量可能会波动，（2）单个干细胞的直系后代可以取代其他干细胞，最终导致单克隆性，（3）隐窝的生命周期可能与干细胞动力学有关。本文的目的是建议一种干细胞和隐窝生长的随机状态依赖性模型，可以解释这些现象并将其链接到一个综合框架中。执行蒙特卡罗模拟以显示与可用数据的一致性。该模型解释了稳态下小肠隐窝的大小分布、干细胞波动和单克隆性转化的观察、中度损伤后隐窝群体的恢复以及隐窝裂变和灭绝的速率。该模型的关键假设是干细胞生长的自动调节控制。 (C) 1997 学术出版社有限公司。
The organization and control of stem cells is a key issue in epithelial cell biology. The small intestinal murine crypt is a useful tissue to study such problems since stem cells are known to be located at specific positions at the bottom of the crypt where they are self maintaining.Recent data suggest, that (1) the number of active stem cells in a crypt can fluctuate, (2) the immediate progeny of a single stem cell can replace other stem cells eventually leading to monoclonality and (3) the life cycle of crypts may be linked to stem cell dynamics.It is the objective of this paper to suggest a stochastic state-dependent model of stem cell and crypt growth which can explain and link these phenomena into one comprehensive framework. Monte Carlo simulations are performed to show consistency with available data. The model explains the size distribution of small intestinal crypts in steady state, the observations of stem cell fluctuations and monoclonality conversion, recovery of the crypt population after moderate damage and the rate of crypt fission and extinction. The key assumption of this model is an autoregulatory control of stem cell growth. (C) 1997 Academic Press Limited.